Method for blood clot lysis



Nov. 14, 1967 J. DELANEY 3,352,303

I METHOD FOR BLOOD CLOT LYSIS Filed July 28, 1965 2 Sheets-Sheet 1 1967 L. J. DELANEY METHOD FOR BLOOD CL-OT LYSIS 2 Sheets-Sheet 2 Filed July 28, 1965 United States Patent ()filice 3,352,303 Patented Nov. 14, 1967 3,352,303 IVE'I'HOD FOR BLOOD CLOT LYSIS Lawrence J. Delaney, Newton Center, Mass. 547 W. Elm t., Brockton, Mass. 02401) Filed July 28, 1965, Ser. No. 475,337 15 Claims. (Cl. 128--24) This invention relates generally to the treatment of cardiovascular disease in humans and, more particularly, to the lysis of blood clots in the blood vessels of living human beings by the direct application to the clot of sonic or supersonic energy vibrations.

The treatment of diseases of the human body by the application of various forms of wave energy has been suggested in the past including the possibility of direct application of vibrational wave energy at sonic or supersonic frequencies for the break-up of calcific deposits associated with the valves of the heart. These techniques generally involve radical surgical procedures for the application of the probe to the affected area and the required duration of application of the sonic energy is substantial. The effect on normal tissue of the energy applied has been found to produce inflammation which increases the danger associated With the procedure.

The present invention is directed to the treatment and cure of a much more widespread form of cardiovascular disease than the specific forms heretofore mentioned. The present invention is based on the discovery that the lysis or dissolution of blood clots wherever they may occur in the body can be achieved using vibrational wave energy. The lysis of the clot is accomplished without necessarily employing radical surgical procedures and in a manner to eliminate any side effects or secondary results which would be dangerous to the patient. As is well known, the occurrence of blood clots anywhere throughout the cardiovascular system is a matter of grave concern for both the patient who suffers from this particular form of disease and the doctor who is to treat him. At present there is no specific therapy available to effectively lyse blood clots.

The present invention provides methods and procedures for the treatment of blood clots in the human body in a manner to completely lyse elements forming the clot into minute particles of subcellular size without the danger of reclotting occurring once disassociation has occurred. The processes of the invention can be practiced in almost all instances by resorting to relatively minor surgical techniques in which the portion of the anatomy upon which the surgery is performed can be selected with relatively complete freedom, thereby permitting the procedure to be practiced without approaching the aggravated portion of the patients cardiovascular system.

The present invention accomplishes the beneficial results described herein by the direct application of sonic, transonic or ultrasonic vibrational wave energy directly to the blood clot at its location in the patients body. It has been determined that a blood clot can be completely lysed by the direct application of tolerable amounts of energy for short periods of time and, in particular, times which are so short that the heating effects normally associated with the application of concentrated wave energy to the human body do not present a significant problem. The lysis of the clot under these conditions has been shown to effect a breakdown of the clotted mass into subcellular particles which show no tendency to reclot or coagulate once the lysis has taken place and thereby permits the procedure to cure the diseased condition without introducing any danger of reclotting or complications due to surgery in the afflicted area.

In practicing the present invention, surgical procedures are involved to expose suitable arteries or veins which are used as points of entry for the insertion of an ultrasonic probe to be guided to the location of the blood clot in order that the wave energy from the end of the probe can be applied directly to the blood clot. Almost all critical areas in the cardiovascular system which are subject to the formation of blood clots can, generally be reached by the insertion of a probe which enters the body at a surgically exposed artery or vein in the limbs where the surgery involved is not significantly traumatic. Generally more than one such approach is available to reach any diseased area and hence an area that is non-vital can be selected for the point of entry. Thus the procedure can be accomplished with a minimum of danger to the patients condition.

Also as a consequence of the accessibility of almost all parts of the cardiovascular system to approach by a remotely inserted probe, the procedures of this invention permit the placement of the end of the probe directly in contact with the blood clot or in extremely close proximity thereto, thus permitting the longitudinal vibration of the end of the probe to propagate wave energy axially from the end of the probe and directly into the blood clot, thereby providing an efficient transfer of energy into the blood clot, to be lysed and a consequent minimum generation of heat in adjoining tissues. The end of the probe can also be advanced into the clot and this coupling is particularly effective for transverse vibration modes of the probe. By virtue of the efliciency of the lysis of the clot under these conditions, the problems normally associated with damage by heat from wave energy applied to the associated normal tissue and the blood vessel in which the probe is placed are avoided.

In accordance with another feature of the invention, a flexible tubular catheter may be inserted in the blood vessel for providing a guiding channel for the subsequent insertion of the ultrasonic probe Within the tubular catheter. This procedure permits the probe to be inserted Within the tubular catheter and guided thereby and thus minimizes the danger of puncturing the wall of the blood vessel.

The use of the tubular catheter also permits the introduction of a radio-opaque dye for the purpose of obtaining an arteriogram to locate the thrombus. An arteriogram before the application of the wave energy from the probe is used to precisely locate the clot. After the application of the wave energy to the clot the effectiveness of the application can be observed and a second application applied if the lysis is not complete. The repeated application of a minimal dosage can be utilized to achieve the ultimate goal of a complete lysis of the thrombus.

Another modification involves employing a tubular probe for the transmissionof the vibrational wave energy with suitable fittings thereon for introducing a liquid, thus a liquid coolant or a radio-opaque dye can be introduced by means of the probe itself thereby simplifying the procedure. The incompressible fluid within such a probe also serves as a wave transmitting medium.

It is the object of this invention to provide, in accordance with the foregoing features and advantages, a method for the lysis of blood clots in vivo in the human body by the application of localized vibrational energy to the blood clot.

The invention will be described with reference to the drawings which illustrate preferred surgical procedures that may be employed in practicing the invention. Other procedures for approaching the occlusion may be used and the invention is accordingly not to be construed as limited to the particular procedures shown.

In the drawings:

FIG. 1 is a detailed view of a probe-catheter insertion through the femoral artery for a proximal approach to a clot in the femoral artery or the aorta.

FIG. 2 is a general view of a probe-catheter insertion through the femoral artery for a distal femoral artery clot.

FIG. 3 is a view showing direct carotid artery system approach in the neck.

FIGS. 4 and 5 are views showing. subclavian-axillarybrachial arterial system distal and proximal approaches respectively; and

FIG. 6 is a general view of a form of suitable apparatus and a modified form of probe.

Referring now to FIGS. 1 and 2, theintroduction of the probe-catheter through the femoral artery will be described. This approach is suitable for sonation of any systemic arterial segment. Using general anesthesia the patient is placed in the supine position. The knees are semi-flexed and the legs are placed in frog position. The groin area having previously been shaved is now scrubbed and painted with zephiran. A vertical skin incision is made from the inguinal ligament, at the point of pulsation of the common femoral artery, and extended distally through the skin and subcutaneous fat. The fascia overlying the adductor canal is incised and allowed to remain open.

At this point the common femoral artery 11 and vein 12 together with the saphenous vein 13 medially, and the Sartorius muscle 14 laterally are visualized in the adductor, canal.

In the proximal approach shown in FIG. 1, the femoral artery 11 is occluded both proximally and distally by the use of bulldog clamp 16 distally and inch umbilical tape 17 threaded through a one inch long, three mm. diameter rubber sleeve proximally. The umbilical tape occlusion is adjustable allowing passage. of a probecatheter 18 by loosening it. A transverse arteriotomy incision 19 is made approximately one-third the circumference of the common femoral through which the probecatheter 18 is introduced. The probecatheter 18 used is radio-opaque, 2.7 mm. in external diameter tapering to 1.6 mm., 5 cm. from the tip. This provides an extremely flexible finger tip for easier manipulation. It is to be noted that the propagation of the sound energy from the end of the probe is thorough and complete throughout the thrombus or embolus, preferably by direct contact .therewith. Because of this fact, the probe diameter does not have to correspond to the vessel size.

In the distal approach of FIG. 2, isolation of the common femoral artery 11 is carriedout. The bulldog clamp 16 is applied proximally and the inch umbilical tape threaded through a one inch long, three mm. diameter rubber sleeve distally 17. An arteriotomy is made and the probe-catheter is introduced in the same manner as in the proximal approach.

To reach a coronary artery, for example, the probecatheter may be introduced using the proximal femoral approach, and threaded up to the region of the aortic sinuses at which time the patient is placed in the left lateral prone position. Test doses of acetylcholine ranging progressively from 0.4 to 0.8 mgm. are injected through the catheter. The object being to prolong diastole to two to four seconds. Between 30 and 40 cc. of contrast material, methylglucamine diatrizoate (Renografin 76) is injected. This will permit a general coronary arteriogram for localizing the thrombus and suitable X-ray pictures for this purpose are taken and developed.

After location of the thrombus, the catheter is ma neuvered into either the anterior or posterior aortic sinuses. At this point the arteriogram films are examined to determine which coronary is occluded and the distance of the occlusion from the ostium.

With this knowledge the probe is advanced to contact the thrombus. The sound energy is now applied for a brief duration such as from 0.5 to 5 seconds. Another arteriogram (post-sonation) is made using 3 to 5 cc. of the contrast material. If the thrombus is not lysed, repeat sonation is carried out with the same dosage.

The carotid system can be approached via either femoral proximal arteriotomy or direct carotid isolation in the neck.

If the femoral approach is to be used, the previously described procedure is carried out and the probe-catheter is threaded up to the aortic arch at which point the direction is modified to enable it to enter either the left common carotid or innominate arteries. After the probecatheter has entered the appropriate artery 20 to 30 cc. of contrast material, methylglucamine diatrizoate (Renografin 76) is injected through the probe-catheter, and anterior-posterior and lateral X-rays are made.

These films will delineate occlusive processes of the innominate artery, the innominate right carotid bifurcation, the common carotid bifurcation and the entire carotid cerebral arterial tree.

Depending on the location of the occlusion, the probecatheter is threaded to it and sonation is applied for brief duration as before described. Repeat arteriography is carried out and after reading the post-sonation arterio' gram, repeat sonations are done if the occlusion has not been completely lysed.

If the direct cervical approach is chosen, the following procedure is carried out as shown in FIG. 3. Under general anesthesia the patient is placed in the supine position, turning his head slightly away from the side to be operated upon. Avoid hyper-extension of the head and neck if there is associated basilar artery insufficiency. A skin incision is madealong the anterior border of the sternmastoid muscle from one inch below the .angle of the jaw to the inferior border of the thyroid gland. The cervical fascia is incised over the carotid bulb, and the sternomastoid muscle is retracted exposing the common carotid artery, the jugular vein posteriorly and the ansa hypoglossi running over the carotid bifurcation. The common carotid artery is occluded proximally by a bulldog clamp 16 and distally by A inch umbilical tape 17 upon which is threaded a one inch long rubber sleeve. A transverse arteriotomy 37 is made in the common carotid artery, one third of the circumference. The probecatheter 18 is then threaded distally to the occlusive process and arteriography and sonation is carried out in the same manner as was described in the femoral approach to the carotid system.

The axillary approach is used for either distal or proximal threading of the probe-catheter to the subclavian axillary-brachial arterial system as shown in FIGS. 4 and 5 respectively.

With the arm abducted and the elbow flexed to 90, the medial surface of the arm is prepped and a two inch incision is made 2 cm. distal to the insertion of the peetoralis major muscle and over the axillary artery. The

brachial plexus is exposed and the axillary artery and.

vein are visualized. The axillary artery is isolated by blunt dissection.

In the distal approach shown in FIG. 4, the axillary artery is occluded by a bulldog clamp 16 proximally and by a shoelace rubber tubing ligature distally 17 An arteriotomy incision is made across the artery and about /3 of its circumference. The probe-catheter 18 is threaded distally, adjusting the distal occlusive ligature 17 for passage and re-occlusion.

After the probe-catheter is within the artery, an arterio gram is made .by injecting 30 cc. of methylglucamine diatrizoate (Renografin 76) after which anterior-posterior and lateral films are made and the point of occlusion located.

The probe-catheter is advanced to the point of occlusion and sonation dosages are administered as before. If occlusion has not been cleared as shown by repeatarteriography, the sonation is repeated in the same doses as originally.

In the proximal approach shown in FIG. 5, the axillary artery is isolated as above and a bulldog clamp 16 placed distally with a shoelace rubber tubing ligature 17 proximally. An arteriotomy 86 is made transversely using Va the circumference of the artery. The probe-catheter 18 is threaded proxirnally to the point above the shoestring rubber ligature and the ligature 17 readjusted to occlude the vessel around the probe-catheter. Methylglucamine diatrizoate (Renografin 76) is injected, and an arteriogram is made as before. After locating the point of occlusion, the probe-catheter is advanced to it, and sonation is carried out. Repeat arteriograms and sonation, if required, are made.

Referring again to FIG. 3, details of the probe-catheter 18 will be described. A thin metallic probe 20 may be employed with the use of flexible tubing 30 as a sheath. The probe 20 may be constructed of stainless steel or Monel metal or any suitable metal like substance which is capable of efficient transmission of sonic or ultrasonic longitudinal vibration waves and, in addition, is flexible enough for the manipulation required in the procedure. The choice of diameter for the probe 20 will be a compromise based on these factors and, in addition, it will generally be found that the larger diameter probes are moreeifective in the lysis of major size blood clots. Obviously the diameter of the probe 20 will be limited to a size less than inner diameter of the blood vessel used to approach the blood clot.

When a radio-opaque fluid is to be employed for an arteriogram or when a fluid coolant or fluid for other purposes is required in the procedure, the flexible catheter 30 may be employed to transmit the fluid. The external end of the catheter 30 may be used for introduction of the fluid by any known technique and after the fluid has been introduced, the flexible metal probe 20 may be threaded through the interior of the catheter 30. Various obvious arrangements for the introduction and control of the fluid flow may be employed at the external end of the catheter 30.

Referring now to FIG. 6, apparatus suitable for use in the invention will be described. An ultrasonic generator 21 of the type generally available commercially is used as the source of electrical energy having control 22 for selecting the output power level and a control 23 for selecting the output frequency. The frequency range should be variable over a substantial interval such as, for example, from 10,000 to 30,000 cycles per second in order to be able to bring the entire vibrational system into resonance under all conditions of operation.

The power output requirement is generally of the order of a few tenths to a few tens of watts and in ordinary cases the lesser power of the order of a few watts is adequate. The generator 21 is preferably of the variable frequency oscillator, power-amplifier type in order to prevent loading effects from changing the frequency of the oscillator.

The generator 21 is connected by means of a cable 24 to a transducer 25 which converts the electrical oscillations into mechanical vibrations at the same frequency. For the use of these vibrations, the transducer is mechanically coupled to a metallic stud 26 Which has a threaded fitting 27 which makes a tight mechanical connection with a corresponding fitting 28 on the end of the probe 20.

As is well known in ultrasonic practice, the entire transducer and coupling assembly is made resonant by being one-half wave length long with a vibrational anti-node located at transition section 29. As is also well understood, the length of the probe 20 from the anti-node 29 should also be an integral multiple of half wavelengths in order to produce the maximum longitudinal deflection at the remote end of the probe 20. The tuning control 23 on the generator 21 may be employed to achieve the resonance anti-node at the end of the probe 20 under operating conditions.

The probe 20' is indicated as of modified construction as compared to the solid rod type probe 20 indicated in FIG. 3. In particular, the probe 20' is tubular having an axial passage 31 running its entire length and communicating with the interior of the fitting 28' at the external end thereof. With this modification, the probe 20' can be connected by means of fitting 28 to a source of fluid supply, such as the radio-opaque dye, and thus serve as a catheter for the introduction of the fluid into the body.

After the arteriogram procedure has been completed, the fitting 28' can be disconnected from the fluid supply and connected to the coupling 27 for the application of vibration energy from the transducer 25. The fluid filled passage 31 acts as an efiicient transmission medium for the longitudinal vibrations inasmuch as fluids are incompressible and relatively loss free for the transmission of vibrations.

While only a few procedures for practicing the invention have been described herein, it Will be apparent that blood clots in any location are susceptible to the procedures of the invention, if they can be exposed to ultrasonic vibrations. As used herein, ultrasonic includes the range of frequencies, including high sonic, transonic and low ultrasonic ranges and the use of any of these terms should be considered to be generic to all such frequencies. The invention, accordingly, is not limited to the particular details of the described embodiments but is defined by the scope of the appended claims.

I claim:

1. The method of lysis of blood clots in blood vessels in vivo by the application of vibrational wave energy comprising the steps of opening a blood vessel that communicates with the location of the blood clot, inserting a probe into the opening in the blood vessel, threading the probe through the blood vessel to advance the distal end thereof until the distal end of the probe is in the vicinity of the blood clot, and propagating vibrational energy through said probe to be applied to the blood clot from said distal end.

2. The method according to claim 1 in which said probe has suflicient transverse flexibility to traverse intricate pathways through the blood vessels to locate said distal end in the vicinity of the blood clot and is capable of propagating throughout its length longitudinal vibration waves to be coupled to the medium in contact with said distal end.

3. The method according to claim 1 in which said probe is a long, thin metal rod and said vibrational energy is propagated therethrough from an electromechanical transducer coupled to the proximal end of said rod outside the body of the patient.

4. The method according to claim 1 and including the step of selecting the frequency of said vibrational energy to produce an anti-node approximately at the distal end of said probe.

5. The method of lysis of blood clots in blood vessels in vivo by the application of vibrational wave energy directly to the blood clot comprising the steps of opening a blood vessel that communicates with the location of the blood clot, inserting a probe into the opening in the blood vessel, threading the probe through the blood vessel to advance the distal end thereof until the distal end of the probe is in contact with the blood clot and propagating vibrational energy through said probe to be applied to the blood clot in contact with said distal end.

6. The method according to claim 5 in which said probe has suflicient transverse flexibility to traverse intricate pathways through the blood vessels to locate said distal end at the blood clot and is capable of propagating throughout its length longitudinal vibration waves to be coupled to the medium in contact with said distal end.

7. The method according to claim 5 in which said probe is a long, thin metal rod and said vibrational energy is propagated therethrough from an electromechanical transducer coupled to the proximal end of said rod outside the body of the patient.

8. The method according to claim 5 and including the step of selecting the frequency of said vibrational energy to produce an anti-node approximately at the distal end of said probe.

9. The method of lysis of blood clotsin vivo -compris ing the steps of surgically exposing a blood vessel which provides a communicating channel to the location of the blood clot, making an incision in the exposed blood vessel, inserting a tubular flexible catheter into said blood vessel through said incision, threading the catheter through the blood vessel to the vicinity of the blood clot, threading through said catheter a probe which is capable of propagating vibrational wave energy,'injecting a small quantity of liquid radiation contrast agent through the catheter, locating the relative positions of the distal end of said probe and the blood clot by arteriography, advancing the probe until the distal end contacts the blood clot, propagating vibrational wave energy of predetermined frequency, power and duration through said probe, repeating arteriography to determine if lysis of the blood clot is complete and repeating the propagation, if necessary, of vibrational wave energy through'said probe to obtain complete lysis of the blood clot.

10. The method according to claim 9 in which said catheter is highly flexible and said probe has sufiicient transverse flexibility to transverse intricate pathways through the blood vessels guided within said catheter to locate the distal end of said probe at the blood clots, the probe being capable of propagating longitudinal vibration waves throughout its length to be applied to the blood clot in contact with said distal end.

11. The method according to claim 9 in which said probe is a long, thin metal rod and said vibrational energy is propagated therethrough from an electromechanical transducer coupled to the proximal end of said rod outside the body of the patient.

12. The method according to claim 9 and including the step of selecting the frequency of said vibrational energy to produce an anti-node approximatelyat the distal end of said probe.

13.- The method of lysis of blood clots in vivo comprising lysing the clots by the step of applying sonic vibration energy to the blood clot by a continuous propagation path which couples from a source outside the body sufiicient energy into the blood ,clot to cause lysis of the clots.

14. The method of lysis of a blood clot in vivo comprising lysing the clots by the step of applying sonic vibration energy to the blood clot with adequate energy to disperse the bloodclot and with the energy localized at the blood clot and of such magnitude as to avoid adverse effect on adjacent tissue.

15. The method of claim 14 in which the propagation path for applying said sonic energy to the blood clot is a tubular metal probe having continuous liquid medium in the tubular passage of said probe.

References Cited UNITED STATES PATENTS 2,283,285 5/1942 Pohlman 128---24 2,407,690 9/ 1946 Southworth 12824 2,893,395 7/1959 Buck 128-349 FOREIGN PATENTS 540,428 4/ 1922 France.

LAWRENCE W. TRAPP, Primary Examiner. 

13. THE METHOD OF LYSIS OF BLOOD CLOTS IN VIVO COMPRISING LYSING THE CLOTS BY THE STEP OF APPLYING SONIC VIBRATION ENERGY TO THE BLOOD CLOT BY A CONTINUOUS PROPAGATION PATH WHICH COUPLES FROM A SOURCE OUTSIDE THE BODY SUFFICIENT ENERGY INTO THE BLOOD CLOT TO CAUSE LYSIS OF THE CLOTS. 